In-vitro and in-vivo comparisons of high versus low concentrations of inhaled epoprostenol to adult intubated patients.

BACKGROUND: Inhaled epoprostenol (iEPO) has been shown to reduce pulmonary artery pressure and improve oxygenation. iEPO is mainly delivered via a syringe pump with feed tubing connected to a vibrating mesh nebulizer with high or low formulation concentration delivery. METHODS: An in vitro study and a two-period retrospective case-control study were implemented. The in vitro study compared iEPO delivery via invasive ventilation at low concentrations of 7.5, and 15 mcg/mL and high concentration at 30 mcg/mL, to deliver the ordered dose of 30 and 50 ng/kg/min for three clinical scenarios with predicted body weight of 50, 70 and 90 kg. While in the clinical study, adult patients receiving iEPO via invasive ventilation to treat refractory hypoxemia, pulmonary hypertension, or right ventricular failure were included. 80 patients received low concentration iEPO at multiple concentrations (2.5, 7.5, and 15 mcg/mL, depending on the ordered dose) from 2015 to 2017, while 84 patients received high concentration iEPO at 30 mcg/mL from 2018 to 2019. RESULTS: In the in vitro study, there were no significant differences in aerosol deposition between high vs low concentrations of iEPO at a dose of 50 ng/kg/min. In the clinical study, age, gender, ethnicity, and indications for iEPO were similar between high and low concentration groups. After 30-120 min of iEPO administration, both delivery strategies significantly improved oxygenation in hypoxemic patients and reduced mean pulmonary arterial pressure (mPAP) for patients with pulmonary hypertension. However, no significant differences of the incremental changes were found between two delivery groups. Compared to low concentration, high concentration delivery group had better adherence to the iEPO weaning protocol (96% vs 71%, p < 0.001), fewer iEPO syringes utilized per patient (5 [3, 10] vs 12 [6, 22], p = 0.001), and shorter duration of invasive ventilation (6 [3, 12] vs 9 [5, 18] days, p = 0.028). Intensive care unit length of stay and mortality were similar between two groups. CONCLUSION: Compared to low concentration delivery of iEPO, high concentration iEPO via a vibrating mesh nebulizer maintained clinical benefits and increased clinician compliance with an iEPO weaning protocol, required less medication preparation time, and shortened duration of invasive ventilation.

Prone positioning for patients intubated for severe acute respiratory distress syndrome (ARDS) secondary to COVID-19: a retrospective observational cohort study.

BACKGROUND: The role of repeated prone positioning in intubated subjects with acute respiratory distress syndrome caused by COVID-19 remains unclear. METHODS: We conducted a retrospective observational cohort study of critically ill intubated patients with COVID-19 who were placed in the prone position between March 18, 2020 and March 31, 2020. Exclusion criteria were pregnancy, reintubation, and previous prone positioning at a referring hospital. Patients were followed up until hospital discharge. The primary outcome was oxygenation assessed by partial pressure of oxygen/fraction of inspired oxygen ratio (Pao2/Fio2) ratio. A positive response to proning was defined as an increase in Pao2/Fio2 ratio ≥20%. Treatment failure of prone positioning was defined as death or requirement for extracorporeal membrane oxygenation (ECMO). RESULTS: Forty-two subjects (29 males; age: 59 [52-69] yr) were eligible for analysis. Nine subjects were placed in the prone position only once, with 25 requiring prone positioning on three or more occasions. A total of 31/42 (74%) subjects survived to discharge, with five requiring ECMO; 11/42 (26%) subjects died. After the first prone positioning session, Pao2/Fio2 (mean (standard deviation)) ratio increased from 17.9 kPa (7.2) to 28.2 kPa (12.2) (P<0.01). After the initial prone positioning session, subjects who were discharged from hospital were more likely to have an improvement in Pao2/Fio2 ratio ≥20%, compared with those requiring ECMO or who died. CONCLUSION: Patients with COVID-19 acute respiratory distress syndrome frequently responded to initial prone positioning with improved oxygenation. Subsequent prone positioning in subjects discharged from hospital was associated with greater improvements in oxygenation.

Effects of Inhaled Epoprostenol and Prone Positioning in Intubated Coronavirus Disease 2019 Patients With Refractory Hypoxemia.

OBJECTIVES: To evaluate the effects of inhaled epoprostenol and prone positioning, individually and in combination in mechanically ventilated patients with coronavirus disease 2019 and refractory hypoxemia. DESIGN: Retrospective study. SETTING: Academic hospital adult ICUs. PATIENTS: Adult patients who received inhaled epoprostenol and prone positioning during invasive ventilation were enrolled. Patients were excluded if inhaled epoprostenol was initiated: 1) at an outside hospital, 2) after prone positioning was terminated, 3) during extracorporeal membrane oxygenation or cardiopulmonary resuscitation, and 4) with Pao2/Fio2 greater than 150 mm Hg. INTERVENTIONS: Inhaled epoprostenol and prone positioning. RESULTS: Of the 43 eligible patients, 22 and seven received prone positioning and inhaled epoprostenol alone, respectively, prior to their use in combination, Pao2/Fio2 was not different pre- and post-prone positioning or inhaled epoprostenol individually (89.1 [30.6] vs 97.6 [30.2] mm Hg; p = 0.393) but improved after the combined use of inhaled epoprostenol and prone positioning (84.0 [25.6] vs 124.7 [62.7] mm Hg; p < 0.001). While inhaled epoprostenol and prone positioning were instituted simultaneously in 14 patients, Pao2/Fio2 was significantly improved (78.9 [27.0] vs 150.2 [56.2] mm Hg, p = 0.005) with the combination. Twenty-seven patients (63%) had greater than 20% improvement in oxygenation with the combination of inhaled epoprostenol and prone positioning, and responders had lower mortality than nonresponders (52 vs 81%; p = 0.025). CONCLUSIONS: In critically ill, mechanically ventilated patients with coronavirus disease 2019 who had refractory hypoxemia, oxygenation improved to a greater extent with combined use of inhaled epoprostenol and prone positioning than with each treatment individually. A higher proportion of responders to combined inhaled epoprostenol and prone positioning survived compared with nonresponders. These findings need to be validated by randomized, prospective clinical trials.